rs628871
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_018900.4(PCDHA1):c.2394+62983T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000068 in 912,304 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000027 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000076 ( 3 hom. )
Consequence
PCDHA1
NM_018900.4 intron
NM_018900.4 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.193
Publications
5 publications found
Genes affected
PCDHA1 (HGNC:8663): (protocadherin alpha 1) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA3 (HGNC:8669): (protocadherin alpha 3) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA6 (HGNC:8672): (protocadherin alpha 6) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA8 (HGNC:8674): (protocadherin alpha 8) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA9 (HGNC:8675): (protocadherin alpha 9) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA2 (HGNC:8668): (protocadherin alpha 2) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA4 (HGNC:8670): (protocadherin alpha 4) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA7 (HGNC:8673): (protocadherin alpha 7) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
PCDHA5 (HGNC:8671): (protocadherin alpha 5) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BS2
High Homozygotes in GnomAdExome4 at 3 gene
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PCDHA1 | NM_018900.4 | c.2394+62983T>A | intron_variant | Intron 1 of 3 | ENST00000504120.4 | NP_061723.1 | ||
| PCDHA3 | NM_018906.3 | c.2394+48076T>A | intron_variant | Intron 1 of 3 | ENST00000522353.3 | NP_061729.1 | ||
| PCDHA6 | NM_018909.4 | c.2394+21182T>A | intron_variant | Intron 1 of 3 | ENST00000529310.6 | NP_061732.1 | ||
| PCDHA8 | NM_018911.3 | c.2394+7952T>A | intron_variant | Intron 1 of 3 | ENST00000531613.2 | NP_061734.1 | ||
| PCDHA9 | NM_031857.2 | c.2394+778T>A | intron_variant | Intron 1 of 3 | ENST00000532602.2 | NP_114063.1 | ||
| PCDHA2 | NM_018905.3 | c.2388+54315T>A | intron_variant | Intron 1 of 3 | ENST00000526136.2 | NP_061728.1 | ||
| PCDHA4 | NM_018907.4 | c.2385+42095T>A | intron_variant | Intron 1 of 3 | ENST00000530339.2 | NP_061730.1 | ||
| PCDHA7 | NM_018910.3 | c.2355+14929T>A | intron_variant | Intron 1 of 3 | ENST00000525929.2 | NP_061733.1 | ||
| PCDHA5 | NM_018908.3 | c.2352+27540T>A | intron_variant | Intron 1 of 3 | ENST00000529859.2 | NP_061731.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PCDHA1 | ENST00000504120.4 | c.2394+62983T>A | intron_variant | Intron 1 of 3 | 1 | NM_018900.4 | ENSP00000420840.3 | |||
| PCDHA3 | ENST00000522353.3 | c.2394+48076T>A | intron_variant | Intron 1 of 3 | 1 | NM_018906.3 | ENSP00000429808.2 | |||
| PCDHA6 | ENST00000529310.6 | c.2394+21182T>A | intron_variant | Intron 1 of 3 | 1 | NM_018909.4 | ENSP00000433378.1 | |||
| PCDHA8 | ENST00000531613.2 | c.2394+7952T>A | intron_variant | Intron 1 of 3 | 1 | NM_018911.3 | ENSP00000434655.1 | |||
| PCDHA9 | ENST00000532602.2 | c.2394+778T>A | intron_variant | Intron 1 of 3 | 1 | NM_031857.2 | ENSP00000436042.2 | |||
| PCDHA2 | ENST00000526136.2 | c.2388+54315T>A | intron_variant | Intron 1 of 3 | 1 | NM_018905.3 | ENSP00000431748.1 | |||
| PCDHA4 | ENST00000530339.2 | c.2385+42095T>A | intron_variant | Intron 1 of 3 | 1 | NM_018907.4 | ENSP00000435300.1 | |||
| PCDHA7 | ENST00000525929.2 | c.2355+14929T>A | intron_variant | Intron 1 of 3 | 1 | NM_018910.3 | ENSP00000436426.1 | |||
| PCDHA5 | ENST00000529859.2 | c.2352+27540T>A | intron_variant | Intron 1 of 3 | 1 | NM_018908.3 | ENSP00000436557.1 |
Frequencies
GnomAD3 genomes 0.0000267 AC: 4AN: 149596Hom.: 1 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
149596
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000760 AC: 58AN: 762708Hom.: 3 Cov.: 11 AF XY: 0.0000792 AC XY: 28AN XY: 353564 show subpopulations
GnomAD4 exome
AF:
AC:
58
AN:
762708
Hom.:
Cov.:
11
AF XY:
AC XY:
28
AN XY:
353564
show subpopulations
African (AFR)
AF:
AC:
0
AN:
14724
American (AMR)
AF:
AC:
0
AN:
890
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
4560
East Asian (EAS)
AF:
AC:
0
AN:
3508
South Asian (SAS)
AF:
AC:
1
AN:
15200
European-Finnish (FIN)
AF:
AC:
0
AN:
14864
Middle Eastern (MID)
AF:
AC:
0
AN:
1454
European-Non Finnish (NFE)
AF:
AC:
56
AN:
682862
Other (OTH)
AF:
AC:
1
AN:
24646
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.469
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Exome Hom
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome 0.0000267 AC: 4AN: 149596Hom.: 1 Cov.: 32 AF XY: 0.0000411 AC XY: 3AN XY: 72958 show subpopulations
GnomAD4 genome
AF:
AC:
4
AN:
149596
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
72958
show subpopulations
African (AFR)
AF:
AC:
0
AN:
40934
American (AMR)
AF:
AC:
1
AN:
14878
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3410
East Asian (EAS)
AF:
AC:
0
AN:
5168
South Asian (SAS)
AF:
AC:
0
AN:
4748
European-Finnish (FIN)
AF:
AC:
0
AN:
10354
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
3
AN:
66840
Other (OTH)
AF:
AC:
0
AN:
2042
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Hom
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
Hom.:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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